Copper-Catalyzed Asymmetric Nucleophilic Opening of 1,1,2,2-Tetrasubstituted Donor–Acceptor Cyclopropanes for the Synthesis of α-Tertiary Amines
Catalytic asymmetric transformation of donor-acceptor cyclopropanes (DACs) has been proven to be a highly valuable and robust strategy to construct diverse types of enantioenriched molecules. However, the use of 1,1,2,2-tetrasubstituted DACs to form products bearing quaternary stereocenters remains a long-term unsolved challenge. Here, we report the copper-catalyzed asymmetric aminative ring opening of tetrasubstituted alkynyl DACs that delivers a myriad of α-tertiary amines with high levels of enantioselectivities. The alkyne, amine, and ester moieties within the products enable diverse further applications, including the asymmetric synthesis of bioactive molecules. Mechanistic studies indicate that the zwitterionic intermediate bearing a copper-acetylide unit plays a key role in the process, which represents a new mode for achieving catalytic asymmetric transformation of DACs.
Authors
- Shouang Lan
- Xinqiang Fang (ORCID: https://orcid.org/0000-0001-8217-7106)
- Defu Luo
- Jinggong Liu (ORCID: https://orcid.org/0000-0001-7755-2186)
- Siyu Shi (ORCID: https://orcid.org/0000-0001-9010-7431)
- Cheng‐Zhi Gu (ORCID: https://orcid.org/0000-0003-3728-7298)
- Lili Zhao (ORCID: https://orcid.org/0000-0003-2580-6919)
- Shuang Yang (ORCID: https://orcid.org/0000-0002-5573-5632)
- Chengyang He (ORCID: https://orcid.org/0000-0002-7157-463X)
- Chao Xu (ORCID: https://orcid.org/0000-0002-9678-4772)
- Qinqin Cui
- Shengyu Huang
Institutions
- Shihezi University (CN)
- Fujian Normal University (CN)
- Guangdong Provincial Hospital of Traditional Chinese Medicine (CN)
- Fujian Institute of Research on the Structure of Matter (CN)
- Chemical Synthesis Lab (SG)
- University of Chinese Academy of Sciences (CN)
- State Key Laboratory of Structural Chemistry
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-12-26
- DOI
- https://doi.org/10.1021/jacs.4c14944
- Citations
- 20
- Primary Topic
- Cyclopropane Reaction Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 5.00
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Ministry of Science and Technology of the People's Republic of China
- Natural Science Foundation of Fujian Province